Ischemic heart disease (IHD) is the number one cause of death in western societies. Rapid, noninvasive, early detection of myocardial underperfusion would be important for timely institution of therapy, but no method to date has provided reliable, high-resolution detection. MRI is a noninvasive technique with excellent soft tissue resolution For IHD, however, it is hampered by the lack of intrinsic contrast. With specific contrast agents, MRI would enable early detection of perfusion abnormalities. Existing agents, however, are not specific enough nor retained long enough to allow stress-coupled MRI of perfusion. We have designed and synthesized effective new agents. The most promising, the water-soluble "ELGAVIST," is the most likely to get commercialized. The goal of our Phase I project, now near completion, was the small-scale study of "ELGAVIST" efficacy in the in vivo dog model of acute myocardial ischemia followed by reperfusion, with and without dobutamine-induced pharmacologic stress. We are proud to report complete success in Phase I with the goal of demonstrating clinically relevant in vivo efficacy of "ELGAVIST" ally achieved, albeit within the limited scope of Phase I. Now we propose a more detailed Phase ll study, with aims for toxicity, pharmacokinetics, clearence, and broadened stress models in dogs. The results should establish the clinical potential of "ELGAVIST", without serious present competition, for early diagnosis of IHD, with a market potential larger than that of Thallium or Cardiolite. Thus Phase II should enhance already existing industrial interest in "ELGAVIST", leading to Phase III commercialization. PROPOSED COMMERCIAL APPLICATIONS: Ischemic heart disease is the number one cause of death in the USA and other western societies. To date no reliable technique is available that would detect early signs of this disease noninvasively and with sufficient tissue resolution. MRI, in conjunction with a pharmacologic, stress test and the contrast agent "Elgavist", can achieve this. This Phase II proposal will enable a successful Phase III commercialization of this agent whose potential market is enormous and without serious present competition.